We recently discovered a novel protein related to Barrier-to-autointegration factor (BAF), which we named BAF-Like (BAF-L). BAF-L interacts with BAF, a conserved chromatin protein important for nuclear assembly, and with LAP2beta and MAN1, two membrane-anchored members of the LEM-domain family of nuclear proteins. Mutation of a third LEM protein, emerin, leads to Emery Dreifuss Muscular Dystrophy (EDMD), a disease that affects heart, skeletal muscle and tendons. Interestingly, BAF-L is not detectable in skeletal muscle or heart, two tissues affected by EDMD, suggesting that BAF-L may help protect tissues lacking emerin. We found that BAF-L interacts with mixed lineage leukemia 3 (MLL3), a member of a family of) proteins involved in transcriptional regulation. We hypothesize that BAF-L may be involved in regulating transcription through MLL3. To test this hypothesis, we will study the interactions of BAF-L with BAF, LAP2 and MLL3 in vitro and in vivo. We will construct a collection of single missense mutations in BAF-L to map the regions of interaction on this protein for LAP2, BAF, and MLL3. We will use several biochemical methods, such as co-immunoprecipitations, pulldowns, and microtiter binding assays, to study BAF-L's biochemical interactions. We will also look at BAF-L interaction with MLL3 in vivo, by studying the localization and interactions of these proteins in cell culture. This project will serve to elucidate the role of BAF-L in the nucleus and will shed light on the biochemical complexes formed by BAF-L at the nuclear envelope. Additionally, the central roles of undergraduate students in the proposed research will enhance student interest in the biological sciences and in pursuing graduate studies in basic biomedical research.